NEUROPHYSIOLOGY DATABASE OF INBRED MUTANT STRAINS

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Neurosensory evaluation of defined gene mutations in inbred strains of mice is an essential component of the genetic analysis of brain and behavior, and a critical tool in assessing responses to pharmacological treatment. The specific aims of this project are to develop and implement rapid, high-throughput electrophysiologic survey methods and an open electronic reference database containing standardized neurophysiological evaluation of inbred strains and mutants, including surface cortical EEG, depth-recorded hippocampal EEG, visual evoked potentials, and brainstem auditory evoked potentials, in awake and behaving mice. The specific aims include: 1) A technological component, involving development of lighter-weight, higher- electrode density epidural and depth electrode arrays for chronic implantation. Current techniques will be enhanced by implementation of non-traumatic, flexible zero-insertion force microconnectors and calibrated, region-specific placement. Electrophysiological data will be acquired digitally, combined with split-screen digital video, and programs to rapidly display and share online over the internet will be implemented. 2) A quantitative data analysis component, involving application of spectral and topological analysis of spontaneous electrocorticograms and averaged evoked potentials to catalog inbred strains. 3) A phenotypic screening standards component: Multi-parametric studies will be performed to assess variability related to diurnal rhythm, time of day, and repeated sampling; age and behavioral state; and characterization of technical artifacts in order to optimize reproducibility and validation of all basal and evoked data samples. 4) An instructional component: all technqiues will be standardized and methods for quantitative analysis and screening will be fully detailed and disseminated for adoption by all NIH mutagenesis centers and other laboratories. 5) A scientific database and informatics component: Storage and retrieval of all raw and analyzed data on inbred strains will be deposited in an open reference database accessible from a dedicated website over the Internet, and summary results published. Following validation, data on specific mutants screened for individual investigators will be available by consent shortly after study. The reference data on inbred strains and defined mutants from multiple centers will be initiated in a common access database, allowing laboratories to subsequently deposit, retrieve, and even reanalyze reference data from mice screened by all centers. Hyperlinks will be created with other databases. This project will provide the framework for normative data to be used for comparative electrophysiological, behavioral and experimental pharmacology on inbred mouse strains and defined gene mutations.